The prevalence of atherosclerotic cardiovascular disease in southwestern American Indians compared to non-Indian populations is significantly lower. In addition, American Indians have lower values of serum cholesterol compared to non-Indian controls. The metabolism of low density lipoprotein and lipoprotein cholesterol composition were investigated to help characterize these differences. Autologous LDL, radiolabelled in the peptide component, was reinjected into volunteers to study LDL kinetics. There were significant differences in the following parameters between Indians and Caucasian controls. The absolute synthetic rate of apoprotein LDL was significantly lower in the southwestern American Indians. This was accompanied by a lower value of apo-LDL and a lower value of LDL cholesterol in the Indians. In addition, the Indians had significantly higher values of high density lipoprotein cholesterol compared to Caucasian controls. These results provide a possible explanation of the relationship between the lower incidence of coronary artery disease seen amongst southwestern American Indians and may help explain the very high prevalence of cholesterol cholelithiasis in this population.